We have previously shown that Met5-enkephalin-Arg6-Phe7 (YGGFMRF) is metabolized by dipeptidyl carboxypeptidase and aminopeptidase. In this study we have searched for an effective enzyme inhibitor that is capable of crossing the blood brain barrier and blocking the inactivation of YGGFMRF by the dipeptidyl carboxypeptidase in CNS. HOE 498 was found to be a potent inhibitor of this enzyme. This compound was tested for its ability to cross the blood brain barrier. The presence of HOE 498 in rat cerebrospinal fluid (CSF) was demonstrated after I.V. or I.P. injection. The presence of HOE 498 in brain was also demonstrated by the increased recovery of YGGFMRF injected into the brain of rats pretreated I.P. with the inhibitor. Further-more, the recovery of YGGFMRF released from striatal tissue slices was increased in the presence of HOE 498. Whether this inhibitor can potentiate the analgesic effect of YGGFMRF still remains to be studied.